The overall objective of this study is to elucidate pharmacokinetic parameters in methadone maintenance patients. Among the goals are, defining the "fast and slow" metabolizers and observing the effects of dose omission, as well as studying drug-drug interactions. Adult healthy male methadone maintenance subjects were hospitalized for three weeks in a metabolic ward. The daily oral doses ranged from 25 to 90 mg (0.4 to 1.01 mg/kg). The morning predose plasma levels showed average 10% fluctuations during regular drug intake. Subjects receiving equivalent mg/kg doses showed variations in dose to plasma level ratio: 0.4 to 0.6 mg/kg produced plasma levels of 76 to 142 ng/ml, doses of 0.8 to 1.0 mg/kg values of 145 to 247 ng/ml. Apparent plasma half-lives of methadone ranged from 7 to 21 hours. The recovery of drug (M) and its metabolites (Met) ranged from 23 to 52% of the total intake in 24-hour urine collections. There were patterns of diurnal variations in the eight-hour fractions of the 24-hour urine. Some subjects eliminated more of the total base during the peak of plasma level, others during the declining phase. The Met/M ratio also showed diurnal variations but remained fairly constant in individual subjects. On the day of omission of the dose, recovery of total bases in 24-hour urine was about one half of that of a normal day and Met/M ratio increased in nearly all subjects. It appears that marked inter-individual variations exist in the pharmacokinetic parameters of methadone, and it might be possible to delineate "fast" and "slow" metabolizers of methadone. BIBLIOGRAPHIC REFERENCES: Verebely, K. and Kutt, H.: Methadone plasma levels in maintenance patients: The effects of dose omission. Res. Comm. in Chem. Pathol. and Pharmacol., 11:373-386, 1975. Dhar, A.K. and Kutt, H.: Pharmacokinetics of dl-methadone in maintenance subjects in the in-hospital study. Fed. Proc. Vol. 35, 1976 (in press).